Depression is a common and potentially serious complication of Parkinson's disease (PD). Studies show that approximately 40 percent of PD patients are depressed. There is evidence that these patients have deficits in verbal fluency, set shifting, confrontation naming, and memory relative to non-depressed PD patients. Despite the widespread toll on emotional health posed by PD, few studies have undertaken a comprehensive examination of the neural underpinnings of Parkinsonian depression. In this project, we will compare depressed versus non-depressed Parkinson patients to a sample of demographically-matched healthy controls using neuropsychological assessment and magnetic resonance imaging (MRI). Our primary hypothesis is that depression in PD is linked to structural and functional abnormality in dorsal and ventral striatum, amygdala, orbitofrontal cortex, medial frontal cortex, and anterior cingulate. Based on this, we predict that in comparisons with non-depressed PD patients, PD patients with depression will show 1.) significant reductions in the volume of the caudate nucleus, orbitofrontal cortex, medial frontal cortex, anterior cingulate, and amygdala;and 2.) reduced activation on cognitive and emotional tasks known to engage these regions. Our secondary hypothesis is that anti-parkinsonian medications, particularly D2/D3 receptor agonists, will result in elevation in mood and increased activation in these brain regions among depressed PD patients during the performance of cognitive and emotional tasks. To delineate the neural substrates of Parkinsonian depression, each patient and control will undergo neuropsychological testing and structural and functional MRI. We will compare regional brain volume in structures associated with depression and patterns of functional MRI activation during working memory and facial affect processing tasks. Neuropsychological testing and fMRI will be performed "on" and "off dopaminergic pharmacotherapy in PD patients and at two similar time points in the unmedicated control group. The research proposed herein will contribute to our understanding of the neural pathways that underlie depression in PD, the relationship of dysphoria to cerebral activation during cognitive and affective processing, and the effects of dopaminergic pharmacotherapy on brain response in prefrontal and limbic regions.